From the aDepartment of Global Health and Population, Harvard School of Public Health, Boston, MA; bChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; cDepartment of Epidemiology, Harvard School of Public Health, Boston, MA; dDepartment of Nutrition, Harvard School of Public Health, Boston, MA; and eMRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom.
Epidemiology. 2015 Mar;26(2):153-62. doi: 10.1097/EDE.0000000000000234.
The prevalence of overweight and obesity is rising globally and together they constitute a major risk factor for coronary heart disease (CHD). Previous estimates of direct effects of high body mass index (BMI) on CHD did not consider an interaction between BMI and its mediators and did not include inflammatory biomarkers as potential mediators.
We analyzed data from 9 prospective cohort studies with 58,322 participants and 9,459 CHD events and decomposed the total effects into natural direct and indirect effects using a 2-stage regression model. We examined overweight (BMI = 25 to <30 kg/m) separately. We pooled hazard ratios using random-effects models and calculated the percentages of excess relative risk mediated by blood pressure, cholesterol, glucose, fibrinogen and high-sensitive C-reactive protein.
There was no interaction between BMI and its mediators in the multiplicative scale (P < 0.05 for all). Blood pressure was the most important mediator. The percentage of excess relative risk of overweight (versus normal BMI, 20 to <25 kg/m) mediated was 28% for blood pressure, 10% for blood glucose, and 14% for cholesterol. The same percentages for obesity were 37% for blood pressure, 17% for blood glucose, and 6% for cholesterol. The percentage mediated through all three metabolic risk factors together was 47% (95% confidence interval = 33%-63%) for overweight and 52% (38%-68%) for obesity. Fibrinogen mediated 6% to 9% and high-sensitive C-reactive protein mediated 6% to 8% of the excess relative risk for overweight and obese participants.
Metabolic mediators explain about half of the adverse effects of high BMI on CHD. The role of inflammatory and prothrombotic biomarkers is much smaller than that of metabolic factors.
超重和肥胖的患病率在全球范围内呈上升趋势，它们共同构成了冠心病（CHD）的主要危险因素。之前对高体重指数（BMI）对 CHD 的直接影响的估计没有考虑 BMI 与其介质之间的相互作用，也没有将炎症生物标志物作为潜在的介质包括在内。
我们分析了来自 9 项前瞻性队列研究的数据，这些研究共有 58322 名参与者和 9459 例 CHD 事件，并使用两阶段回归模型将总效应分解为自然直接和间接效应。我们分别研究了超重（BMI=25 至<30kg/m）。我们使用随机效应模型汇总危险比，并计算血压、胆固醇、血糖、纤维蛋白原和高敏 C 反应蛋白介导的超额相对风险的百分比。
在乘法尺度上，BMI 与其介质之间没有相互作用（所有 P<0.05）。血压是最重要的介质。超重（与正常 BMI，20 至<25kg/m）的超额相对风险的介导百分比为 28%用于血压，10%用于血糖，14%用于胆固醇。肥胖的相同百分比为 37%用于血压，17%用于血糖，6%用于胆固醇。通过所有三种代谢危险因素共同介导的百分比分别为超重的 47%（95%置信区间=33%-63%）和肥胖的 52%（38%-68%）。纤维蛋白原介导超重和肥胖参与者超额相对风险的 6%至 9%，高敏 C 反应蛋白介导 6%至 8%。
代谢介质解释了高 BMI 对 CHD 的不利影响的一半左右。炎症和促血栓形成生物标志物的作用远小于代谢因素。
